Antipsychotic compounds appear to act by altering the ability of neurotransmitters to change the intracellular concentration of cyclic nucleotides. Our results suggest that the mechanism by which they affect this process is by binding to a calcium-dependent protein (calmodulin) which is found in high concentrations in the central nervous system. This protein has been shown to activate several different enzyme systems, including phosphodiesterase, adenylate cyclase and ATPase. We found that antipsychotic drugs of diverse chemical structure all bind in a highly selective, high affinity manner to calmodulin. Therefore, as predicted, these drugs inhibit each of these enzyme systems by blocking their activation. These results suggest that many of the diverse biochemical actions of antipsychotic agents can be explained by a common mechanism; namely, by binding to calmodulin. In fact, our results suggest that calmodulin may serve as a cellular receptor for antipsychotic compounds. The present work is designed to develop techniques by which we can irreversibly bind antipsychotic drugs to calmodulin. With these techniques we may be able to determine the anatomical localization of this protein and measure its rate of synthesis.